Abstract
Govaniadine (1), a tetrahydroprotoberberine-type alkaloid, is one of the main active constituent isolated from Corydalis govaniana Wall., Papaveraceae, with several biological activities: antinociceptive, anti-urease, and leishmanicidal. Some articles reporting tetrahydroprotoberberine and structurally related alkaloids cytotoxicity prompted us to evaluate the influence of compound 1 on cellular viability in two different cell lines: human hepatoma carcinoma (HepG2) and human embryonic kidney (HEK-293T) and its permeation across the human colon carcinoma cell line (Caco-2). Cellular viability reduction of compound 1 was observed between 30 and 100 μM (HepG2) and between 70 and 100 μM (HEK-293T). However, the effects were weaker than those in the positive controls (T-2 toxin and camptothecin). Prior to proceed the transport studies, a method for compound 1 quantification in Hank’s Balanced Salt Solution medium was developed and validated by LC-MS/MS. The two calibration curves were linear over the concentration range of 6.3–200 nM and 0.2–10 μM. The apparent permeability coefficient for absorptive transport was 20.6 ± 3.9 × 10−6 cm/s, indicating compound 1 crossed the cell monolayer by passive diffusion and it was not subjected to active efflux.
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Acknowledgments
This study formed part of a collaborative work within the Research Network Natural Products against Neglected Diseases (ResNetNPND, http://www.resnetnpnd.org/).
Funding
This study was supported by the Sao Paulo Research Foundation (Grant no. 2015/02592-8; 2013/16496-5).
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Conceptualization: LMMM, MB, H-UH, and NPL; formal analysis: LMMM, MB, UR, and RL(S)S; funding acquisition: H-UH and NPL; methodology: LMMM, MB, SK, UR, AA, and RL(S)S; project administration: LMMM, H-U H, and NPL; supervision: AA, H-UH, and NPL; writing—original draft: LMMM; writing—review and editing: MB, H-UH, and NPL.
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Marques, L.M.M., Behrens, M., Kalinina, S. et al. Govaniadine Evaluation of Cytotoxicity and Permeability in Cell Culture. Rev. Bras. Farmacogn. 30, 374–380 (2020). https://doi.org/10.1007/s43450-020-00066-w
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DOI: https://doi.org/10.1007/s43450-020-00066-w